CAMP
Senior University Professor Richard Partchuses
NMR to monitor receptor-toxin interactions. Changes in the numerical
values of proton or carbon chemical shifts are known to occur when
some organic receptor molecules are exposed to donor molecules. The
physical basis for this phenomenon is a change in the electronic and
magnetic environment near the atoms in question as the two molecules
approach each other. Such shifts are being measured by Professor Richard
Partch and graduate student Evon Powell, to determine how well several
receptor molecules having electron deficient aromatic rings bind to
electron rich aromatic rings of some therapeutics (Fig.1)
and other bioactive molecules, including cocaine, that are lethal
when overdosed. Figure 2 shows how the
two rings share
pelectron density in the
charge-transfer mode.

Powell,
with synthesis assistance from Research Associate Dr. Sudha Rani
and undergraduates Allison Jacques and Heather Stokes, prepared
several dinitrobenzene derivatives having powerful charge-transfer
acceptor properties. They have carboxamide and sulfonamide functionalities
and are designed for subsequent covalent attachment to biocompatible,
injectable carrier nanoparticles for use in emergency remediation
of overdoses

The
NMR spectrum of the aromatic protons in one receptor example, N-ethyl-3,5-dinitrobenzene
carboxamide, appear as a triplet centered at 9.1755 ppm and a doublet
centered at 9.9575 ppm. The peaks in both the doublet and triplet
retain the same splitting when a donor like bupivacaine is added.
However, all of the peaks in the multiplets shift by amounts shown
in Table 1. Such shifts can be used
to calculate binding energies of the acceptor-donor complexes, which
are believed to relate to the efficiency of removal of a toxin from
blood. This type of binding depends on relativep
electron
density of aromatic ring systems and is not influenced by water
or other components such as carbohydrates, cholesterol or proteins
in blood.